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Science. 2016 Apr 22;352(6284):453-9. doi: 10.1126/science.aad5978.

RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

Author information

1
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
2
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK. Department of Haematology, University of Cambridge, The Clifford Allbutt Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, UK.
3
Laboratory of Nuclear Dynamics, The Babraham Institute, Cambridge CB22 3AT, UK.
4
Laboratory of Signalling, The Babraham Institute, Cambridge CB22 3AT, UK.
5
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
6
Bioinformatics Group, The Babraham Institute, Cambridge CB22 3AT, UK.

Abstract

Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-μ at the pre-BCR checkpoint.

PMID:
27102483
DOI:
10.1126/science.aad5978
[Indexed for MEDLINE]
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